title: Change in serum ferritin concentration in experimentally induced anemia of chronic inflammation in dogs.
abstract: In veterinary medicine, hyperferritinemia is often observed in dogs with various diseases (e.g., histiocytic sarcoma and immune-mediated hemolytic anemia) without evidence of iron overload. The mechanism underlying hyperferritinemia development is not well understood. Anemia caused by inflammation is termed as anemia of chronic disease (ACD), and experimentally induced ACD is known to cause slight hyperferritinemia. However, almost all these studies were based on short-term acute inflammation. Hepcidin, a protein mainly produced by hepatocytes, is thought to be a key regulator in iron release from reticuloendothelial cells (RECs), and its expression is related to ACD. We hypothesized that in the case of long-term ACD, iron deposition in RECs increases through hepcidin, causing a diachronic increase in serum ferritin levels. In the present study, we used a canine model with repeated subcutaneous administration of turpentine oil every 3 days over a period of 42 days (15 injections) and induced long-term inflammatory conditions; furthermore, we evaluated the change in serum ferritin concentration. Hypoproliferative anemia, bone marrow iron deposition and hypoferremia, which are characteristic of ACD, were observed on administering the turpentine injections. Hepatic iron content, hepatic hepcidin mRNA expression and serum ferritin concentration increased during the early period after turpentine injection, but returned to normal levels later. These results show that experimentally induced long-term ACD caused hypoproliferative anemia without sustained increase in hepcidin expression and did not cause systemic iron overload. Thus, chronic inflammation may not contribute greatly to increase in hyperferritinemia.
authors.affiliation: Department of Small Animal Internal Medicine, School of Veterinary Medicine, Kitasato University, 23-35-1 Higashi, Towada, Aomori 034-8628, Japan.
authors.forename: Seishiro
authors.initials: S
authors.lastname: Chikazawa
authors.forename: Takafumi
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Yasutomo
authors.initials: Y
authors.lastname: Hori
authors.forename: Fumio
authors.initials: F
authors.lastname: Hoshi
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Kanai
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Ito
authors.forename: Koichi
authors.initials: K
authors.lastname: Orino
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Watanabe
authors.forename: Seiichi
authors.initials: S
authors.lastname: Higuchi
mesh_terms: D000740:Anemia / Q000276:immunology / Q000662:veterinary*; D000818:Animals; D001772:Blood Cell Count / Q000662:veterinary; D002097:C-Reactive Protein / Q000032:analysis; D004283:Dog Diseases / Q000276:immunology*; D004285:Dogs; D005260:Female; D005293:Ferritins / Q000097:blood*; D064451:Hepcidins / Q000235:genetics / Q000276:immunology*; D007249:Inflammation / Q000276:immunology / Q000662:veterinary*; D008099:Liver / Q000276:immunology*; D008297:Male; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary
chemical_list: D064451:Hepcidins; D012313:RNA; D002097:C-Reactive Protein; D005293:Ferritins